Synchronous bilateral testis tumor: mixed germ cell and theca cell tumors

Synchronous bilateral testis tumors of different histologic types are rare. All previous cases have demonstrated germ cell tumors on both sides. The simultaneous appearance of a germ cell tumor and a contralateral non-germ cell tumor has not been reported. We herein report a thirty-four-year-old man who presented with a mixed non-seminomatous germ cell tumor of the left testis and theca cell tumor of the right testis.     

Germ cell neoplasms of the testis

Testicular germ cell neoplasia, a disease predominantly of young men, is, for unknown reasons, increasing in incidence. Cryptorchidism, a prior testicular germ cell tumor, a family history of testicular germ cell tumors, and somatosexual ambiguity syndromes remain well-established risk factors. Intratubular germ cell neoplasia of the unclassified type represents the common precursor to the great majority of testicular germ cell tumors, and its identification in testicular biopsies reliably identifies those patients who will often progress to an invasive lesion. Seminoma appears to represent the invasive derivative of intra-tubular germ cell of neoplasia of the unclassified type; problematic variants include seminomas with tubular, granulomatous, and edematous patterns. Spermatocytic seminoma is an essentially nonmetastasizing neoplasm unless complicated by the rare development of a sarcomatous component. Embryonal carcinomas usually occur admixed with other germ cell tumor types. The combination of positivity for placental alkaline phosphatase and negativity for epithelial membrane antigen can assist in the distinction of embryonal carcinomas from somatic carcinomas. The treatment of clinical stage I patients with nonseminomatous germ cell tumor with "surveillance only" may be contraindicated depending on features that include the proportion of embryonal carcinoma and the presence of lymphovascular invasion in the orchiectomy specimen. It is important to be aware that pure, mature teratomas in postpubertal patients may be associated with metastases of teratomatous or nonteratomatous type Yolk sac tumor is characterized by numerous patterns including glandular, myxomatous, sarcomatoid, hepatoid, and parietal variants. Choriocarcinomas classically have a biphasic pattern of syncytiotrophoblast and cytotrophoblast; trophoblastic proliferations lacking a biphasic pattern also occur but are difficult to classify unless this category is broadened. Mixed germ cell tumors, consisting of two or more different elements, are quite common. The polyembryoma is a distinctive, well-organized form of mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor.     

Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease: more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis

A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal tumors in Ollier's disease. The related condition of multiple enchondromatosis and hemangiomas (Maffucci's syndrome) is well known for its malignant potential, developing both mesodermal and non-mesodermal tumors. Along with other authors, we support the concept of two variants of the same disease with a predisposition to development of tumors from various germ layers.     

Metastases from testicular carcinoma. Study of 78 autopsied cases

The necropsy records of 78 patients with histologically proved germ cell tumors of the testis, who died as a direct result of their malignant disease, were reviewed to determine the usual modes of spread, distribution of metastasis, the histologic characteristics of the metastatic foci as compared with the morphology of the primary tumor and the specific cause of death. The sites of metastases in order of decreasing frequency for all cases were lung, retroperitoneal lymph nodes, liver, mediastinal lymph nodes, brain, kidney, gastrointestinal tract, bones, adrenals, peritoneum and spleen. The absence of metastases solely in the anterior mediastinum without involvement of other mediastinal nodes (middle/posterior) strongly supports the premise for a primary extragonadal origin whenever the anterior mediastinum alone is involved with malignant disease having the histologic appearance of a primary germ cell tumor. The histologic features of the metastatic lesions were usually similar in nature to those of the primary tumor except for seminoma in which the metastatic lesions proved to be of a different histologic pattern in almost one third of the patients dying from the disease. It should be axiomatic that whenever a patient with seminoma fails to respond appropriately to radiotherapy that his treatment be immediately discontinued and that appropriate biopsies be obtained to substantiate the histologic pattern present.     

Cryptosporidium parvum--propagation of oocyst in neonatal calves

A retrospective analysis of treatment of 8 children aged 5 to 13 years with intracranial germ cell tumors (3 germinomas, 5 nongerminomatous cell tumors) is reported. All patients were initially operated. Five of them underwent total or incomplete removal of the tumor. After surgery 2 children received radiotherapy alone (1 germinome, 1 nongerminomatous germ cell tumors) and 5 (2 germinomas, 3 nongerminomatous germ cell tumors) combined radio- and chemotherapy. One patient (choriocarcinoma) didn't receive any adjuvant treatment after total tumor removal. All 3 children with germinomas show complete remission for 29, 40 and 93 months. Of 5 patients with nongerminomatous germ cell tumors in 2 the duration of remission was 22 and 53 months and 3 relapsed 4, 12 and 24 months after treatment. The data presented demonstrate that the treatment results of intracranial germ cell tumors in children depend on histologic type of the tumor. Thus, precise tumor type determination is most important for choosing optimally adequate treatment approach.     

The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo

A case of ovarian mixed germ cell tumor in a 44-year-old woman was examined. The tumor was well circumscribed, measured 15 x 11 x 10 cm and appeared solid and partly cystic on the cut surface. Light microscopic examinations revealed that the tumor was composed of four different neoplastic germ cell elements, intermingled with each other. They are: (i) choriocarcinoma, immunohistochemically positive for human placental lactogen (hPL) and human chorionic gonadotropin (hCG); (ii) dysgerminoma, positive for placental alkaline phosphatase; (iii) endodermal sinus tumor positive for alpha-fetoprotein (AFP); and (iv) mature teratoma. Among these histological types, dysgerminoma occupied more than 50% of the neoplasm. The patient was diagnosed as a stage la ovarian mixed germ cell tumor and was subsequently treated with chemotherapy. A second-look laparotomy after completion of chemotherapy revealed no residual tumors in the abdomen and the patient is alive and well 15 months after operation. This is the fourth reported case of ovarian mixed germ cell tumor arising in patients over 40 years old.     

Systemic mast cell disease associated with primary ovarian mixed malignant germ cell tumor

A 12-year-old girl with a mixed malignant germ cell tumor of the ovary, treated by surgery and chemotherapy, developed systemic mast cell disease (SMCD) approximately 3 months after chemotherapy. Hematologic malignancies have previously been noted in patients with mediastinal germ cell tumors but this is the first report of a primary ovarian germ cell neoplasm associated with SMCD.     

Endodermal sinus tumor and embryonal carcinoma of the ovary in a 53-year-old woman

BACKGROUND: Germ cell tumors, the most common ovarian malignancies in females under the age of 21, are rare in older women. We report an unusual case of a mixed embryonal carcinoma and endodermal sinus germ cell tumor in a perimenopausal patient and review the differential diagnosis and management of these malignancies with respect to age. CASE: A 53-year-old woman complaining of irregular menses and pelvic pain was found to have a large pelvic mass and a positive pregnancy test. Subsequent investigation revealed a large left adnexal mass, and an elevated beta-HCG and alpha-AFP. At laparotomy, a mixed germ cell tumor was found. The patient was treated with multiagent chemotherapy and currently is without evidence of disease. CONCLUSION: Although rare, the diagnosis of germ cell tumor should be considered in older women presenting with a large pelvic mass. The treatment and prognosis is similar regardless of age, except that reproductive-sparing surgery is not a priority in the older patient.     

Structural characterization with circular dichroism of native and modified human serum albumin

OBJECTIVE: Extragondal germ cell tumors are rare and have a high affinity for the midline structures. Herein we describe a young, male patient with a retroperitoneal primary tumor. METHODS/RESULTS: The unorthodox form of presentation of germ cell tumors corroborates their embryologic gonadal origin which is distant from the site of presentation. CONCLUSION: The diagnostic algorithm, chemotherapeutic and surgical treatment guidelines utilized in the management of primary gonadal germ cell tumors with retroperitoneal involvement remain applicable in this rare form of presentation.     

Possible common origin of alpha-fetoprotein- and human chorionic gonadotropin--secreting cells in intracranial germ cell tumor. Case report

A primary intracranial germ cell tumor in a 16-year-old boy secreted both alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). The tumor, located in the right thalamus, contained germinomatous, trophoblastic, and endodermal sinus components. To identify AFP- and HCG-secreting cells, germ cells from the surgical specimen were cultured in vitro. These cultured cells secreted AFP and HCG for 10 weeks, and immunohistochemical studies showed that some of the cells secreted both AFP and HCG. These findings suggest that multipotential germ cells migrate to the encephalic region and may become germ cell tumors containing various types of tissue.     

Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome

An 8-year-old boy presented with precocious puberty and a mediastinal mass. A computer search showed that this rare presentation is most common with germ cell tumor of the mediastinum in children with Klinefelter syndrome. The tumor was completely resected after preoperative chemotherapy, and the patient is well 2 years after the operation. In patients with Klinefelter syndrome, germ cell tumors are 50 times more common than in patients without Klinefelter syndrome, usually contain nonseminomatous elements, present at an earlier age, and are seldom testicular in location.     

Molecular pathogenesis and prognostic factors in testicular tumor

Aim of this review article was to critically analyse the recently described zytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosome i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (Cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromsomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in research for prognosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it also will define new approaches to classification and management of germ cell tumors.     

Unusual metastasis of renal cell carcinoma. A case report with review of the literature

BACKGROUND: The occurrence of metastasis of renal cell carcinomas in the head and neck region is extremely rare. Metastasis in the larynx, hypopharynx, and the nasal sinuses has been reported. We report here about a 55-year-old female with metastasis in the soft palate and tonsil, which occurred 10 years following tumor nephrectomy. RESULTS AND CONCLUSIONS: The incidence of metastasis in renal cell carcinomas can be observed even many years following initial curative treatment of the primary tumor. Although rare in the region of the head and neck, they can often be mistaken for benign tumors such as hemangiomas or inflammatory tissue. The treatment of choice is radical surgical resection.     

Neuroblastoma arising in testicular teratoma

One case of neuroblastoma arising in an adult immature testicular teratoma is described, with multiple systemic metastases, a partial response to intensive chemotherapy and a swift recurrence leading to death. Such instances of prevailing neuroblastoma with systemic metastases, have only seldomly been reported hitherto. Because of the teratoma and the focal presence of intratubular germ cell neoplasia of unclassified type, we think this tumor must be indeed of germ cell derivation.     

Prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations

OBJECTIVE: To describe the characteristic cytologic features of fine needle aspirates (FNAs) of primary extragonadal germ cell tumors (PEGCTs). STUDY DESIGN: Thirteen patients with PEGCTs, including 2 seminomas, 2 mixed germ cell tumors, 3 immature teratomas, 1 choriocarcinoma and 5 yolk sac tumors (YSTs) were studied. The final diagnosis of PEGCT in all cases was established by histologic examination of the tumor tissues. Fine needle aspiration was done on either the primary tumor or metastatic foci. The aspirates were stained with one of the Romanovsky stains and Papanicolaou stain. RESULTS: Each type of PEGCT has its own morphologic characteristics. In seminoma, the tumor cells are large and noncohesive, with one to several distinct nucleoli; some lymphocytes are also present. YSTs show many pleomorphic cells with vacuoles in the cytoplasm and nuclei; tumor cells frequently aggregate in a microglandular or papillary pattern. Choriocarcinoma consists of syncytiotrophoblasts and cytotrophoblasts. The former are very large cells with eosinophilic cytoplasm, one to several nuclei and distinct nucleoli; the latter are medium-sized cells with vacuolated, basophilic cytoplasm and eccentric nuclei. Immature teratomas are composed of a mixture of cell types, including elongated epithelioid cells, mesenchymal cells and many large, naked, amorphous nuclei with a homogeneous chromatin pattern. Diagnosis of mixed germ cell tumor is difficult but can be made if two or more subtypes of tumor cells are observed in the FNA. CONCLUSION: Cytologic examination of FNAs of primary or metastatic lesions of PEGCTs, stained either with Romanovsky or Papanicolaou stain, is of diagnostic value for such diseases. The use of immunochemistry can help to confirm the cytologic impression.     

Clinical relevance of the i(12p) marker chromosome in germ cell tumors

BACKGROUND: Germ cell tumors in men are curable at all stages and are among the most sensitive of all cancers to chemotherapy. An isochromosome of the short arm of chromosome 12, i(12p), has been reported to be a frequent marker of these tumors and to have diagnostic and prognostic significance. PURPOSE: We evaluated the possible association between this cytogenetic marker and clinical outcome for men with germ cell tumors. METHODS: One hundred seventy-eight germ cell tumor samples from 150 men were studied using conventional and molecular cytogenetic techniques. Of these samples, 171 were evaluable. Patient characteristics, disease stage, treatment outcome, and disease status were correlated with the observed cytogenetic changes. In addition, 28 biopsy specimens obtained from 28 patients with tumors of uncertain histogenesis were evaluated to determine whether the presence of i(12p) could serve as a diagnostic marker of a germ cell origin for these tumors. RESULTS: Of the 171 evaluable tumor accessions, 101 (59%) yielded abnormal karyotypes. i(12p) was determined to be present in 79 of the 101 (79%) abnormal karyotypes, which were derived from all cell types and primary sites. An abnormal karyotype was more frequently obtained from nonseminomatous tumors (91/137 [81%]) than from seminomas (10/34 [30%] [P < .001]). Tumors resulting in a cytogenetic failure were more likely to respond completely to chemotherapy than tumors with an abnormal karyotype (P = .004). i(12)p copy number was not associated with response or survival. Fluorescence in situ hybridization using a chromosome 12 centromere-specific probe detected i(12p) in 47 of 47 tumors (100%) already shown to have i(12p) by cytogenetic analysis and in 13 of 49 tumors (27%) exhibiting either an abnormal karyotype or a cytogenetic failure. One or more copies of i(12p), excess 12p copy number, or a deletion on the long arm of chromosome 12 was found in seven of 28 (25%) midline tumors of uncertain histogenesis, thus establishing a diagnosis of a germ cell tumor in these patients. One partial and five complete responses were observed in these seven patients. Only two partial responses were seen in the 17 patients who had no detectable germ cell tumor-related cytogenetic marker (P = .009). CONCLUSIONS: i(12p) is a highly nonrandom chromosomal marker seen in about 80% of male germ cell tumors with evaluable cytogenetic abnormalities. The presence of this isochromosome has diagnostic and possibly prognostic importance for patients with these tumors. IMPLICATIONS: Cytogenetic studies of germ cell tumors in prospective clinical treatment trials are warranted to define more precisely the relationship between histologic subtype, serum tumor marker production, and prognosis.     

Testicular tumors: clinically relevant histological findings

Testicular germ cell neoplasms affect young men in the prime of life. Although the overwhelming majority are malignant, they are curable. In addition to the stage of the disease and the presence of serum markers, there are important pathological changes that have clinical significance. These include (1) the cell type, (2) the amount of the component, and (3) the presence or absence of vascular invasion. Pure embryonal carcinoma or embryonal carcinoma in excess of 80% in a mixed tumor and vascular/lymphatic invasion are high-risk factors as they are predictors of relapse. These factors should be recognized by the pathologist and should be taken into account by the oncologist when selecting the management of a patient with a germ cell tumor of the testis.     

Differential expression of protooncogenes in human germ cell tumors of the testis

BACKGROUND: It has been suggested that tumorigenesis of the germ cell tumor of the testis includes abnormal and developmentlike differentiation of primordial germ cells to several mature type tumors. METHODS: To clarify roles of protooncogenes in the unique tumorigenic mechanism in the human germ cell tumor, the authors examined the expression of 15 protooncogenes in human primary germ cell tumors of the testis with Northern blot analyses. RESULTS: Fifteen (94%) of 16 seminomas and 5 (83%) of 6 embryonal carcinomas had a significant levels of N-myc expression, whereas they did not express two receptor type protooncogenes, c-erbB-1 and c-erbB-2. In contrast, some immature teratomas had a high level of c-erbB-1 expression, and an advanced case showed a significant level of c-erbB-2 expression. Immature teratomas did not show N-myc expression. Higher levels of c-mos expression were observed in several cases of seminomas and embryonal carcinomas. Expression of c-Ki-ras or N-ras was observed in all histologic subgroups and normal testes. CONCLUSION: A significant level of N-myc expression may be essential for undifferentiated tumors including seminoma and embryonal carcinoma, whereas c-erbB-1 and possibly c-erbB-2 may have important roles in the differentiated tumors such as immature teratoma. These results suggest that some of the protooncogene expression may be switched critically during the differentiation from seminomas or embryonal carcinomas to the more differentiated-type tumor.     

A Tourette-like syndrome following cardiopulmonary bypass and hypothermia: MRI volumetric measurements

OBJECTIVES: To review the outcome of men with Stage I nonseminomatous germ cell tumors managed with a policy of active surveillance following orchiectomy. METHODS: The clinical records of all men with Stage I nonseminomatous germ cell tumors seen at Royal Prince Alfred Hospital, Australia between 1982 and 1995 were reviewed. Data were obtained concerning the histologic type of tumor, levels of serum tumor markers, relapse and subsequent treatment, and survival. RESULTS: Seventy-seven patients were entered into the active surveillance protocol between 1982 and 1995. With a minimum follow-up of 2 years, 27 (35%) have relapsed, with a median time to relapse of 5 months. Two late relapses occurred at 37 and 57 months after diagnosis. Relapses occurred most commonly in the retroperitoneal lymph nodes, with the lungs the second most common site. Following treatment with chemotherapy and surgery, all patients achieved complete remission, with 1 patient subsequently relapsing and ultimately dying of progressive tumor. One other patient died of acute myeloid leukemia, thought to be secondary to chemotherapy. Overall, 75 patients (97%) remain alive and free of disease. CONCLUSIONS: Active surveillance is a safe and effective approach to the management of Stage I nonseminomatous germ cell tumors. Although most relapses occur within the first 2 years, late relapses may occur.     

Hepatic cavernous hemangioma: appearance on T2-weighted fast spin-echo MR imaging with and without fat suppression

OBJECTIVE: The goals of our study were to define the morphologic appearance of cavernous hemangioma of the liver on T2-weighted fast spin-echo MR imaging and to determine if the use of fat suppression may quantitatively and qualitatively modify the MR imaging appearance of cavernous hemangioma. SUBJECTS AND METHODS: Twenty-six patients with cavernous hemangiomas of the liver were prospectively studied with T2-weighted MR imaging with a fast spin-echo technique with and without fat suppression. Thirteen patients had known hemangiomas for more than 2 years, with no change in size or morphology during this period. The remaining 13 patients had diagnoses based on dynamic CT and sonography and an absence of change in the morphology and size of their lesions during follow-up of more than 6 months (range, 6-12 months) after the MR imaging studies. Values for signal intensity and contrast-to-noise (C/N) ratios in cavernous hemangiomas that were obtained with and without fat suppression were compared. Images were qualitatively analyzed separately at identical level and window settings by two interpreters for morphologic features of cavernous hemangiomas. RESULTS: No significant difference was found between signal intensity values obtained using the fat-suppressed fast spin-echo MR imaging technique (5.62 +/- 1.14 [SD]) and those obtained without fat suppression (5.51 +/- 1.23). Values for C/N ratios obtained with the fat-suppressed fast spin-echo MR imaging technique (20.13 +/- 7.63) were significantly superior to those obtained without fat suppression (16.59 +/- 5.31) (p < .001). On T2-weighted fast spin-echo MR imaging without fat suppression, 100% of cavernous hemangiomas were hyperintense relative to the spleen, 90% had well-defined and sharp margins, 55% were isointense to CSF, and 76% were homogeneous. Without fat suppression, 34% of cavernous hemangiomas showed the combination of isointensity to CSF, well-defined margins, and homogeneity. On T2-weighted fast spin-echo MR imaging with fat suppression, all cavernous hemangiomas showed this same combination of features. CONCLUSION: Seventy-six percent of hepatic cavernous hemangiomas were homogeneous on T2-weighted fast spin-echo MR imaging, and 55% were isointense to CSF. However, only 34% of hepatic cavernous hemangiomas showed typical features. Although fat suppression significantly increased the C/N ratio of cavernous hemangiomas of the liver, fat suppression did not affect their morphologic appearance on T2-weighted fast spin-echo MR imaging.